Phytochemical profiling and ameliorative effects of Achillea cretica L. on rat model of endometriosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Achillea cretica (AC) is a medicinal plant emphasized for treatment of gynecological disorders and pathological symptoms similar to endometriosis in traditional Persian medicine. Since information about its chemical constituents is limited, the aim of this study is to investigate phenolic composition of AC extract as well as its effect on experimental model of endometriosis. MATERIALS AND METHODS: RP-HPLC-PDA-ESI-MS/MS analysis was used for the determination of polyphenolic compounds. Endometriosis was induced in rats by suturing of uterus segments to abdominal wall of same rat, after eight weeks when the model was induced, it was followed by 28 days of treatment with 100, 200, and 400 mg/kg/day of hydroethanolic extract of the plant. Blood samples and implanted tissues were collected in the final day, and area of foci, tumor necrosis factor-α, vascular endothelial growth factor, interleukin-6, and serum total thiol molecules were measured and compared with positive group (0.2 mg/kg/day letrozole) and control group (solvent of extract: normal saline). Implanted tissue sections of the sacrificed rats were also assessed histopathologically. RESULTS: Nine polyphenolic compounds were identified in AC extract including 7 flavonoids and 2 phenolic acids. Plant extract decreased area of foci and cytokine levels in serum and local tissue. Histopathological assessments confirmed the effectiveness of treatments by decreasing the thickness of epithelial layer and increasing the infiltration of leukocytes into this layer. Doses of 100 mg/kg and 400 mg/kg of extract showed better effects in comparison with the dose of 200 mg/kg in reduction of cytokine levels and size of implanted tissue. Extract and letrozole did not demonstrate significant effect on thiol level. CONCLUSION: AC aerial extract may be a favorable medicine for management of endometriosis by modulating inflammatory cytokines; however, further studies are needed for more conclusive and reliable decision about its efficacy and safety.

Development of a Novel Anti-Obesity Compound with Inhibiting Properties on the Lipid Accumulation in 3T3-L1 Adipocytes

Background: Obesity as a developing global challenge can be characterized by increase in adipocyte number and size arising from adipogenesis. Control of adipogenesis, as a potential strategy, can prevent and manage obesity. So far, the effectiveness of herbal medicine and active ingredients therapies for obesity and metabolic syndrome treatment has been investigated. In this study, a novel combination of berberine, catechin, and capsaicin was developed, and their effect on 3T3-L1 adipocytes was investigated. Mthods: The effect of active ingredient on the cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Adipocytes were treated with various concentrations of berberine (3 and 6.25 µM), catechin (6.25 and 12.5 µM), and capsaicin (6.25 and 12.5 µM) alone and in combination. Results: All active ingredients did not affect the cell viability by MTT assay at different concentrations. The dual and triple combinations of three active ingredients showed excellent potential as anti-obese without any toxicity. The inhibitory effect of berberine, catechin, and capsaicin on the differentiation of 3T3-L1 preadipocytes was found to be dose-dependent. These results indicate that catechin in both doses may have a stronger effect than the two other active ingredients on the intracellular lipid accumulation. Also, the triple combination of the aforementioned ingredients showed better responses than their dual combination. Conclusion: This work is the first report to simultaneously investigate these three active ingredients in a single, dual, and triple formats. The berberine, catechin, and capsaicin co-treatment inhibits the adipogenesis during the differentiation process. This compound can be a prospective therapy for obesity and relevant diseases such as dyslipidemia.

Efficacy of topical application of standardized extract of Tragopogon graminifolius in the healing process of experimental burn wounds.

Tragopogon graminifolius DC. is a perennial plant from the family Asteraceae which grows in West parts of Iran. Several biological activities like antimicrobial, antioxidant and anti-inflammatory effects are reported for the plant. The aim of this study was to assess the wound healing activity of standardized extract from T. graminifolius (TG) aerial parts. Topical standardized TG extract with 5% and 10% concentrations in eucerine base was assessed for its healing properties on second degree burn in rats during a 14-day period. Biomarkers of oxidative damage including total antioxidant power, lipid peroxidation and total thiol molecules of the skin tissue samples were also evaluated. Results showed that 10%TG had the best efficacy with 80 ±â€¯3% wound closure and tissue repair in comparison to negative control (p < 0.05). Significant reduction of tissue oxidative stress biomarkers was also observed. Histological analyses confirmed wound healing activity of TG extract, as well. Considering the antioxidative stress and anti-inflammatory activities of TG, explained by the high content of phenolic compounds of the plant, standardized TG extract could be considered as a natural remedy for the treatment of burn wounds. Further clinical studies are suggested to confirm the effectiveness of TG as a wound healing agent.

Manipulation of molecular pathways and senescence hallmarks by natural compounds in fibroblast cells.

Aging contributes to an increased risk of developing a number of neurodegenerative and chronic disorders, predominantly related to oxidative stress (OS) and defects in the antioxidant balance. This study focused on the antisenescence effect of four plant species (Falcaria vulgaris, Ixiolirion tataricum, Ajuga chamaecistus, and Scabiosa flavida) on H2 O2 -induced premature senescence in rat NIH3T3 fibroblasts, which were found to be rich in effective phytochemicals with traditional ethnobotanical backgrounds. Plant materials were collected, identified, and extracted. To determine the viability of NIH3T3 cells, an MTT assay was conducted. The levels of OS markers and the senescence-associated ß-galactosidase (SA-ß-GAL) activity were analyzed by the Elisa reader. The cell cycle pattern was evaluated by flow cytometry. The expression of senescence-related inflammatory cytokines and the molecules involved in aging signaling pathways were investigated using the real-time reverse transcription polymerase chain reaction (RT-PCR). H2 O2 treatment decreased cell viability and increased lipid peroxidation (LPO) and the reactive oxygen species (ROS) in NIH3T3s. However, S. flavida exhibited low cytotoxicity, reduced OS and SA-ß-GAL activities in NIH3T3 cells compared with the H2 O2 -treated group. I. tataricum was the second best plant, although it was more toxic to NIHT3T cells. S. flavida decreased G0/G1 arrest and facilitated the G2/M transition of NIH3T3s, also downregulated the expression of p38, p53, p16, and the related inflammatory mediators. S. flavida potentially modulated senescence-associated hallmarks in fibroblasts exposed to H2 O2 , thus it may inhibit the aging process via controlling the OS. Therefore it is a promising candidate for future antiaging explorations.

Evaluation of anti-tyrosinase activity of Allium ursinum extracts and their metal complexes.

BACKGROUND: A. ursinum is found to contain high levels of some beneficial phenolic and poly phenolic compounds were found to be effective in scavenging DPPH radicals and tyroinase inhibition. The aim of this study was to evaluate the anti-tyrosinase and antioxidant activity of three different extracts from the ultrasound-assisted method and their metal complexes from A. ursinum to discover new candidates for food additives, cosmetic and pharmaceutical products. METHODS: Water, 70% ethanol and absolute ethanol extract of Allium ursinum and their man- ganese and zinc-complexes were characterized by FT-IR and UV-Vis spectra and their antioxidant and anti- tyrosinase activity determined using DPPH radical scavenging and mushroom tyrosinase assay. RESULTS: The antioxidant activity of the water extract was superior to other samples, while the 70% ethanol extract exhibited the highest anti-tyrosinase activity. Metal complex formation of the extracts led to a signifi- cantly lower antioxidant effect. The tyrosinase inhibition strongly related to the metal ion and extraction sol- vent. All the zinc complexes had lower anti-tyrosinase activity than their extracts, while the manganese com- plex of the water and absolute ethanol extracts exhibited higher anti-tyrosinase activity than related extracts. CONCLUSIONS: This study shows that Mn complex of A. ursinum extracts, based on the solvent extraction, could increase tyrosinase inhibition activity and could be a good candidate for intended cosmetic applications and food additives.

Bio-guided fractionation and isolation of active component from Tragopogon graminifolius based on its wound healing property.

ETHNOPHARMACOLOGICAL RELEVANCE: Tragopogon graminifolius (T. graminifolius) from Asteraceae family has been used as a remedy in Persian traditional medicine for the treatment of various disorders such as wound healing. AIM OF THE STUDY: The purpose of this study is to investigate the compounds of T. graminifolius, which are responsible for its wound healing activity. MATERIALS AND METHODS: The experiment was performed in three phases; each phase consisted of fractionation of extracts followed by scratch assay. The results of the scratch assay were expressed using scratch closure index (SCI), representing the contraction of scratch. RESULTS: In phase I, Ethyl acetate fraction (E) showed the maximum SCI (61.7 ±â€¯3.5) that was selected for more fractionation in the next phase. In phase II, 12 fractions were obtained and labeled as fractions E- A to L, respectively. Based on the SCI of fractions, EF (SCI=68.9 ±â€¯0.6) was the most active fraction in phase II and selected for further fractionation in phase III. In phase III, 8 fractions were resulted by fractionation of EF and labeled as EF- 1-8. Fraction EF5 with the highest SCI (30.8 ±â€¯3.0) was the most effective fraction and Luteolin was the main component. Luteolin significantly improved viability of fibroblast cells and increased cell population that was accompanied by decreased cell apoptosis. Luteolin-induced cell number increase in the S and G2M phases of the cell cycle, further confirms the proliferative effect of this compound. CONCLUSION: The results showed that the total extract and fractions of T. graminifolius stimulate proliferation and migration of skin fibroblast cells and Luteolin is one of the active compounds responsible for these effects.

Evaluation of phytochemicals, antioxidant and burn wound healing activities of Cucurbita moschata Duchesne fruit peel.

OBJECTIVES: Cucurbita moschata Duchesne (pumpkin) is a well-known plant with several pharmacological effects. The aim of the present study was to assess burn wound healing activity of C. moschata peel extract (CE). Also, standardized CE was assessed for antioxidant activity and antibacterial effects against major pathogens of burns. MATERIALS AND METHODS: Healing properties of topical preparation of 10% and 20% concentrations of CE were assessed on second degree burn in rats during a 14-day period as well as histological studies, total antioxidant power, lipid peroxidation and total thiol content of skin tissue samples. RESULTS: Radical scavenging IC50 and ferric-reducing antioxidant power value were 4.015±0.20 mg/ml and 142.63±2.65 mmol Fe2+/g, respectively. Total mucilage content was 13.8%. The optimal results were obtained by 20% CE that showed 90.80±5.86 % wound closure and tissue repair as well as significant reduction of tissue oxidative stress biomarkers. Histological analyses confirmed wound healing activity of pumpkin peel extract. CONCLUSION: Considering the high mucilage content of the plant, providing a moist environment for wound, C. moschata peel extract could be a natural remedy for treatment of burns. Further clinical studies are suggested to confirm C. moschata peel extract as a wound healing agent.

Blockage of both the extrinsic and intrinsic pathways of diazinon-induced apoptosis in PaTu cells by magnesium oxide and selenium nanoparticles.

Diazinon (DZ) is an organophosphorus insecticide that acts as an acetylcholinesterase inhibitor. It is important to note that it can induce oxidative stress, lipid peroxidation, diabetic disorders, and cytotoxicity. Magnesium oxide (MgO) and selenium nanoparticles (Se NPs) showed promising protection against oxidative stress, lipid peroxidation, cytotoxicity, and diabetic disorders. Therefore, this study was conducted to explore the possible protective mechanisms of MgO and Se NPs against DZ-induced cytotoxicity in PaTu cell line. Cytotoxicity of DZ, in the presence or absence of effective doses of MgO and Se NPs, was determined in human pancreatic cancer cell line (PaTu cells) after 24 hours of exposure by using mitochondrial activity and mitochondrial membrane potential assays. Then, the insulin, proinsulin, and C-peptide release; caspase-3 and -9 activities; and total thiol molecule levels were assessed. Determination of cell viability, including apoptotic and necrotic cells, was assessed via acridine orange/ethidium bromide double staining. Furthermore, expression of 15 genes associated with cell death/apoptosis in various phenomena was examined after 24 hours of contact with DZ and NPs by using real-time polymerase chain reaction. Compared to the individual cases, the group receiving the combination of MgO and Se NPs showed more beneficial effects in reducing the toxicity of DZ. Cotreatment of PaTu cell lines with MgO and Se NPs counteracts the toxicity of DZ on insulin-producing cells.

Experimental and Pathalogical study of Pistacia atlantica, butyrate, Lactobacillus casei and their combination on rat ulcerative colitis model.

This study evaluated the effects of Pistacia atlantica (P. atlantica), butyrate, Lactobacillus casei (L. casei) and especially their combination therapy on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced rat colitis model. Rats were divided into seven groups. Four groups received oral P. atlantica, butyrate, L. casei and the combination of three agents for 10 consecutive days. The remaining groups were negative and positive controls and a sham group. Macroscopic and histopathological examinations were carried out along with determination of the specific biomarker of colonic oxidative stress, the myeloperoxidase (MPO). Compared with controls, the combination therapy exhibited a significant alleviation of colitis in terms of pathological scores and reduction of MPO activity (55%, p=0.0009). Meanwhile, the macroscopic appearance such as stool consistency, tissue and histopathological scores (edema, necrosis and neutrophil infiltration) were improved. Although single therapy by each P. atlantica, butyrate, and L. casei was partially beneficial in reduction of colon oxidative stress markers, the combination therapy was much more effective. In conclusion, the combination therapy was able to reduce the severity of colitis that is clear from biochemical markers. Future studies have to focus on clinical effects of this combination in management of human ulcerative colitis. Further molecular and signaling pathway studies will help to understand the mechanisms involved in the treatment of colitis and inflammatory diseases.

Dual targeting of TNF-α and free radical toxic stress as a promising strategy to manage experimental polycystic ovary.

CONTEXT: It is now clear that oxidative stress (OS) and chronic low-grade inflammation are two main pathways involved in polycystic ovary syndrome (PCOS) pathogenesis. Therefore, simultaneous targeting of these pathways by means of carvedilol and Semelil (ANGIPARS™), as established medicines with dual anti-cytokine and anti-oxidant potential may be a therapeutic alternative approach to the current treatments. OBJECTIVE: The objective of this study is to study the protective effects of carvedilol and ANGIPARS™ on inflammatory and oxidative response in hyperandrogenism-induced polycystic ovary (PCO). MATERIALS AND METHODS: The murine model of PCO was induced by letrozole (1 mg/kg/d; orally) and effective doses of carvedilol (10 mg/kg/d; orally) and ANGIPARS™ (2.1 mg/kg/d; orally) were administrated for 21 d in PCO and non-PCO healthy rats. Ovarian folliculogenesis, sex hormones concentrations, OS, inflammatory, and metabolic biomarkers were assessed in serum and ovaries. RESULTS: PCO rats exhibited ovarian cystogenesis which was preserved by the application of carvedilol and ANGIPARS™. In comparison with controls, decreased level of the total antioxidant power (TAP) and higher levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in serum and ovaries (2.41 ± 0.67 versus 0.72 ± 0.11; and 0.17 ± 0.04 versus 0.05 ± 0.01; 5.48 ± 1.30 versus 10.56 ± 0.77; and 7.06 ± 1.94 versus 17.98 ± 0.98; p < 0.05, respectively) were detected in PCO rats. Moreover, the PCO rats exhibited hyperandrogenism due to a 3.7-fold increase in serum testosterone concentration (35.04 ± 3.17 versus 131.09 ± 13.24; p < 0.05) along with a 2.98-fold decrease in serum progesterone (6.19 ± 0.40 versus 18.50 ± 1.03; p < 0.05) and 5.2-fold decrease in serum estradiol (9.30 ± 0.61 versus 48.3 ± 2.10; p < 0.05) when compared with those of the control group. However, similar to the control group, normal levels of OS markers and sex hormones were detected in ANGIPARS™ and carvedilol co-treated PCO rats. Besides, when compared with controls, increased levels of TNF-α (770.75 ± 42.06 versus 477.14 ± 28.77; p < 0.05) and insulin (1.27 ± 0.10 versus 0.36 ± 0.05; p < 0.05) in PCO rats were significantly inhibited by carvedilol and ANGIPARS™ co-treatment. DISCUSSION AND CONCLUSION: We evidenced the beneficial effects of carvedilol and ANGIPARS™ in PCO, which underpin the new alternative approach in using these kinds of medicines in female reproductive disorders.

Biochemical and histopathological evidence on the beneficial effects of Tragopogon graminifolius in TNBS-induced colitis.

CONTEXT: Tragopogon graminifolius DC. (Compositae) (TG) has been proposed as an efficacious remedy for gastrointestinal ulcers in Iranian traditional medicine. OBJECTIVE: The present study evaluates the efficacy of TG on experimental colitis and the responsible mechanisms. MATERIALS AND METHODS: After induction of IBD by 2,4,6-trinitrobenzenesulfonic acid (TNBS), rats received standardized ethanol extract of TG aerial part at 20, 30, or 50 mg/kg/d orally. After 12 d, the rats were sacrificed and the colon was removed and assessed for macroscopic and microscopic changes. Also, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), total antioxidant capacity, myeloperoxidase (MPO), and lipid peroxidation (LPO) were measured in the colon homogenate. RESULT: TG extract significantly reduced macroscopic and microscopic scores of colitis with ED50 values of 23 and 39 mg/kg, respectively. MPO was significantly reduced in all plant extract groups with an ED50 value of 41 mg/kg. The ED50 values of extract for inhibition of TNF-α and LPO were 44 and 93 mg/kg, respectively. IL-1ß significantly decreased by 50 mg/kg of TG extract (ED50 = 57 mg/kg). Total antioxidant power markedly increased by 50 mg/kg group (ED50 = 43 mg/kg). DISCUSSION: TG exhibited efficacy on TNBS-induced colitis via anti-inflammatory, immunomodulatory, antioxidant, and mucosal healing properties. CONCLUSION: TG possesses promising healing function on colitis. Clinical trials are warranted to prove its efficacy and tolerability in IBD.

Promising effect of Magliasa, a traditional Iranian formula, on experimental colitis on the basis of biochemical and cellular findings.

AIM: To investigate the efficacy of Magliasa, a traditional Iranian formula, on experimental colitis. METHODS: After botanical authentication of herbal ingredients, formulation of Magliasa, quantitative determination of total glucosinolates and total phenolic content, and analysis of the thin layer chromatography profile were performed. Colitis was then induced in male rats by instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in all groups, aside from the Sham group. The experimental groups consisted of: the Sham group that received only normal saline; the Mag-50, Mag-100 and Mag-200 groups, which received 50, 100 and 200 mg/kg per day of Magliasa, respectively; the control group, which received vehicle water orally; the infliximab group, which received infliximab (5 mg/kg per day, subcutaneously); and the Dexa group, which received dexamethasone (1 mg/kg per day, orally). After completing the treatment period (2 wk), the rats were sacrificed, the colon was removed, its macroscopic and microscopic changes were recorded, and tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), total antioxidant capacity, myeloperoxidase (MPO), and lipid peroxidation (LPO) were assessed in colon homogenate. RESULTS: The mean value of total glucosinolates in one gram of Magliasa was 19 ± 1 µmol. The mean value of the total phenolic content was 293.8 ± 17.6 mg gallic acid equivalents per 100 gram of Magliasa. Macroscopic scores were significantly decreased in Mag-100 (1.80 ± 0.58, P = 0.019) and Mag-200 (1.20 ± 0.20, P = 0.001) compared to the control group (3.40 ± 0.24), although some inflammation and hyperemia were evident. Treatment of rats by dexamethasone (0.33 ± 0.21, P < 0.001) and infliximab (0.83 ± 0.31, P < 0.001) remarkably attenuated scores where mild hyperemia was observed macroscopically. In comparison to the control group (4.00 ± 0.32), only Mag-200 (1.60 ± 0.40) showed a significant decrease in colonic histopathological scores (P = 0.005). Minimal mucosal inflammation was observed in the Dexa group (0.67 ± 0.21, P < 0.001). The levels of TNF-α, IL-1ß and MPO were significantly lower in all groups compared to the controls (P < 0.05). A significant decrease in LPO was seen in the Mag-200 (3.27 ± 0.77, P = 0.01) and Dexa (3.44 ± 0.22, P = 0.011) groups in comparison to the control group (6.43 ± 0.61). Only dexamethasone caused a significant increase in antioxidant power in comparison to the control group (346.73 ± 9.9 vs 228.33 ± 2.75, P < 0.001). Infliximab and different doses of Magliasa did not show any remarkable increase in antioxidant capacity (P > 0.05). The effect of Magliasa in all of mentioned parameters, except antioxidant capacity, was dose dependent. CONCLUSION: The effects of Magliasa in TNBS-induced colitis are encouraging and warrant clinical trials for further confirmation.

Anti-aging effects of some selected Iranian folk medicinal herbs-biochemical evidences.

OBJECTIVE(S): In the current study, the effects of selected folk medicinal herbs were evaluated in D-galactose-induced aging in male mice. MATERIALS AND METHODS: Male BALB/c mice were randomly divided into 12 groups composing sham, control, and treated groups. Aging was induced by administration of D-galactose (500 mg/kg/day for 6 weeks). A positive control group was assigned that received vitamin E (200 mg/kg/day). The extract of herbs was prepared, lyophilized, and used in this study. The herbs were administered by gavage for 4 weeks to D-galactose-aged animals at the selected doses (mg/kg/day) as follows: Zingiber officinale (250), Glycyrrhiza glabra (150), Rosmarinus officinalis (300), Peganum harmala (50), Aloe vera (150), Satureja hortensis (200), Teucrium scordium (200), Hypericum perforatum (135) and Silybum marianum (150). One group of animals was assigned as sham and not given D-galactose. RESULTS: At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α), interlukine-1ß (IL-ß), interlukine-6 (IL-6), NF-kappaB (NF-κb), total antioxidant power (TAP), thiobarbituric acid reactive substances (TBARS) as lipid peroxidation (LPO) marker and male sex hormones i.e. testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were measured in the blood. CONCLUSION: These data for the first time indicate significant anti-aging potential of examined herbs. RESULTS showed that D-galactose induces a significant oxidative stress and promotes proinflammatory cascade of aging while all herbs more or less recovered these changes. Among 9 herbal extracts, Silybum marianum showed the best effect in restoring aging changes.

Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles.

Cisplatin (CIS), an anticancer alkylating agent, induces DNA adducts and effectively cross links the DNA strands and so affects spermatozoa as a male reproductive toxicant. The present study investigated the cellular/biochemical mechanisms underlying possible protective effect of selenium nano-particles (Nano-Se) as an established strong antioxidant with more bioavailability and less toxicity, on reproductive toxicity of CIS by assessment of sperm characteristics, sperm DNA integrity, chromatin quality and spermatogenic disorders. To determine the role of oxidative stress (OS) in the pathogenesis of CIS gonadotoxicity, the level of lipid peroxidation (LPO), antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and peroxynitrite (ONOO) as a marker of nitrosative stress (NS) and testosterone (T) concentration as a biomarker of testicular function were measured in the blood and testes. Thirty-two male Wistar rats were equally divided into four groups. A single IP dose of CIS (7 mg/kg) and protective dose of Nano-Se (2 mg/kg/day) were administered alone or in combination. The CIS-exposed rats showed a significant increase in testicular and serum LPO and ONOO level, along with a significant decrease in enzymatic antioxidants levels, diminished serum T concentration and abnormal histologic findings with impaired sperm quality associated with increased DNA damage and decreased chromatin quality. Coadministration of Nano-Se significantly improved the serum T, sperm quality, and spermatogenesis and reduced CIS-induced free radical toxic stress and spermatic DNA damage. In conclusion, the current study demonstrated that Nano-Se may be useful to prevent CIS-induced gonadotoxicity through its antioxidant potential.

Benefit of Aloe vera and Matricaria recutita mixture in rat irritable bowel syndrome: Combination of antioxidant and spasmolytic effects.

OBJECTIVE: To evaluate the beneficial effects of a mixture of Aloe vera (AV) and Matricaria recutita (German chamomile, GC) in an experimental model of irritable bowel syndrome (IBS). METHODS: IBS was induced by a 5-day restraint stress in rats including the groups of control (water), GC (300 mg/kg), loperamide (10 mg/kg), mixed AV and GC (50: 50 at doses of 150, 300 or 450 mg/kg assigned as Mix-150, Mix-300 and Mix-450, respectively) and the sham group which did not receive any restraint stress and was fed with saline. All medications were administered intragastrically by gavage for 7 days, 2 days as pre-treatment followed by 5 days during induction of IBS every day before restraining. RESULTS: The increased tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO) activity, and lipid peroxidation (LPO) in colonic cells in the control group were significantly decreased in the treatment groups. GC inhibited only small bowel transit while the AV/GC mixture delayed gastric emptying at the doses of 150 and 300 mg/kg. The AV/GC mixture also reduced colonic transit and small bowel transit at the dose of 150 mg/kg. CONCLUSIONS: The severity of stress-induced IBS was diminished by the AV/GC mixture at all doses used but not dose-dependently, via inhibiting colonic MPO activity and improving oxidative stress status. The effect of the mixture was more effective than GC alone. The present results support effectiveness of the AV and GC combination in IBS.

Effects of IMOD™ and Angipars™ on mouse D-galactose-induced model of aging.

The aim of this study was to evaluate the effects of two registered herbal drugs called IMOD and Angipars on mouse model. Aging was induced by D-galactose (500 mg/kg) administered to animals for 6 weeks through drinking water. Male BALB/c mice were randomly divided into 5 groups receiving D-galactose (D-galactose, 500 mg/kg) for 6 weeks; positive control (D-galactose [500 mg/kg] for 6 weeks + Vitamin E [200 mg/kg/day] intraperitoneally for 4 weeks); IMOD (D-galactose [500 mg/kg] for 6 weeks + IMOD [20 mg/kg/day] intraperitoneally for 4 weeks), Angipars (D-galactose [500 mg/kg] for 6 weeks + Angipars [2.1 mg/kg/day] by gavage for 4 weeks); and the fifth group that was sham and not given D-galactose. At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α), interlukine-1ß (IL-ß), interlukine-6 (IL-6), Nuclear Factor-kappaB (NF-κb), total antioxidant power (TAP), lipid peroxides (LPO) and male sex hormones i.e. testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were measured in the blood.Results showed that D-Galactose induces a significant oxidative stress and proinflammatory cascade of aging while both IMOD and Angipars recovered all of them. Interestingly, IMOD and Angipars were better than Vitamin E in improving male sex hormones in aged mice. This effect is so important and should be considered as an advantage although it cannot be explained with current knowledge. The conclusion is that IMOD and Angipars have marked anti-aging effect on D-galactose-induced model of aging.

Amelioration of experimental colitis by a novel nanoselenium-silymarin mixture.

BACKGROUND: Silymarin has intracellular antioxidant property and inhibits activation of nuclear factor-κB (NF-κB) in low concentrations and reduces tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6 levels, cyclooxygenase (COX), and angiogenesis. Selenium is one of the necessary trace element nutrients for human and animals. Selenium nanoparticles (nano-Se) have more bioavailability with less toxicity. AIMS: To investigate the combination effect of silymarin and nano-Se on inhibition of NF-κB, proinflammatory cytokines, and oxidative stress biomarkers in the experimental colitis. METHODS: Trinitrobenzene sulfonic acid (TNBS) was used to induce colitis. After TNBS instillation, rats were distributed into six groups, containing silymarin and nano-Se alone or in combination, dexamethasone, negative control with no treatment and the last one was normal sham rats. All drugs were administered for 7 days. Colon samples were scored macroscopically and microscopically. The levels of activated NF-κB, IL-1ß, TNF-α, myeloperoxidase (MPO), lipid peroxidation, protein carbonyl (PC), and the antioxidant power of the colon homogenates were determined. RESULT: A significant decrease in NF-κB activity in treated groups was observed. The levels of TNF-α, IL-1ß, MPO, lipid peroxidation, and PC were reduced and an improvement in antioxidant power of treated groups was seen. Combination of silymarin and nano-Se were more effective than each one alone in improvement of NF-κB, TNF-α, antioxidant power, and lipid peroxidation values, although this difference was not significant in other factors. CONCLUSION: Co-administration of silymarin and nano-Se with a good antioxidant profile and inhibition of NF-κB is a possible candidate for better management of inflammatory bowel disease.

Effects of Melissa officinalis L. on oxidative status and DNA damage in subjects exposed to long-term low-dose ionizing radiation.

The aim of this study was to determine the capability of Melissa officinalis L. (Lemon balm) infusion on improvement of oxidative stress status in radiology staff that were exposed to persistent low-dose radiation during work. The study was a before-after clinical trial performed on 55 radiology staff. They were asked to drink Lemon balm infusion which was prepared like a tea bag twice daily (1.5 g/100 mL) for 30 days. In the plasma, lipid peroxidation, DNA damage, catalase, superoxide dismutase, myeloperoxidase, and glutathione peroxidase activity were measured before and after using Lemon balm infusion.Use of Lemon balm infusion in radiology unit workers resulted in a significant improvement in plasma levels of catalase, superoxide dismutase, and glutathione peroxidase and a marked reduction in plasma DNA damage, myeloperoxidase, and lipid peroxidation. It is concluded that infusion of Lemon balm markedly improve oxidative stress condition and DNA damage in radiology staff when used as a dietary supplement for radiation protection.

Efficacy of Setarud (IMod), a novel drug with potent anti-toxic stress potential in rat inflammatory bowel disease and comparison with dexamethasone and infliximab.

The inflammatory bowel disease (IBD) is an idiopathic, immune-mediated and chronic intestinal condition. In the present study, the effect of Setarud (IMOD), a novel natural drug with known immunomodulatory, anti-inflammatory and antioxidant properties was investigated in experimental colitis in rats and compared with the dexamethasone and infliximab. Immunologic colitis was induced by intracolonic administration of a mixture of trinitrobenzene sulfonic acid (TNBS) and absolute ethanol in male Wistar rats. Animals were divided into 6 groups of sham (normal group), control (vehicle-treated), positive control (dexamethasone 1 mg/kg/day given orally and infliximab 5 mg/kg/day given subcutaneously) and 3 Setarud-treated groups (13.3, 20, 30 mg/kg/day given intraperitoneally). The treatment continued for 14 consecutive days and then animals were decapitated on the day 15 and distal colons were removed for macroscopic, microscopic, and biochemical assays. Biochemical markers, including TNF-alpha, IL-1beta, ferric reducing/antioxidant power (FRAP), myeloperoxidase (MPO) activity and thiobarbitoric acid-reactive substance (TBARS) were measured in the homogenate of colonic tissue. A remarkable reduction in macroscopic and histological damage scores was observed in the animals treated with Setarud. These findings were confirmed by decreased levels of TNF-alpha, interleukin-1beta, MPO activity and TBARS, and raised levels of FRAP in the colon tissue. These observations confirmed the immunomodulatory, anti-inflammatory and antioxidant properties of Setarud in experimental colitis, which was comparable to those of dexamethasone and infliximab.

Prevention of malathion-induced depletion of cardiac cells mitochondrial energy and free radical damage by a magnetic magnesium-carrying nanoparticle.

The present work was designed to examine the effect of a new (25)Mg(2+)-carrying nanoparticle (PMC16) on energy and oxidative stress parameters inside the heart of the rats exposed to acute mild toxic dose of malathion, a widely used organophosphate. Post a single intraperitoneal (ip) injection of malathion (0.25 of LD50), PMC16 at different doses (0.05, 0.1, and 0.2 of LD50) was administered intravenously (iv) as a supplement to standard therapy of atropine and pralidoxime. MgSO(4) was used as another supplement for comparison with PMC16. Oxidative stress biomarkers including lipid peroxidation (LPO) and reactive oxygen species (ROS), antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), ATP/ADP ratio, and Mg in the cardiac cells were determined. Results indicated a significant increase in LPO, ROS, ADP/ATP ratio, and a decrease in Mg post-malathion poisoning in comparison to controls. All of these parameters were improved by use of standard therapy either with MgSO4 or various doses of PMC16. The activities of SOD, CAT, and GPx did not change significantly in the present acute malathion poisoning model and neither MgSO(4) or PMC16 had no considerable improvement on these parameters. Comparing groups that received normal Mg and those of various doses of PMC16, a significant difference was found with the PMC16 (0.2 LD50) group. PMC16 0.2 reduced cardiac cells LPO and ROS of Mal-exposed animals rather than that of MgSO4. PMC16 0.2 was also significantly better than MgSO(4) in improving MAL-induced changes in ADP/ATP ratio and also intracellular Mg levels. This study illustrates that malathion-induced cardiac cells toxicity is improved by administration of Mg as a result of increasing cardiac ATP through active transport of Mg inside the cells. Finally, the results of this study support positive effects of this magnetic Mg nanoparticle carrier but do not confirm its absolute efficacy that remains to be explored by further tests in different animal models and organs before moving to a phase I human trial.